Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado, USA.
Obesity (Silver Spring). 2009 Oct;17(10):1932-41. doi: 10.1038/oby.2009.143. Epub 2009 May 21.
We investigated candidate genomic regions associated with computed tomography (CT)-derived measures of adiposity in Hispanics from the Insulin Resistance Atherosclerosis Study Family Study (IRASFS). In 1,190 Hispanic individuals from 92 families 3 from the San Luis Valley, Colorado and San Antonio, Texas, we measured CT-derived visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and visceral:subcutaneous ratio (VSR). A genome-wide association study (GWAS) was completed using the Illumina HumanHap 300 BeadChip (approximately 317K single-nucleotide polymorphisms (SNPs)) in 229 individuals from the San Antonio site (stage 1). In total, 297 SNPs with evidence for association with VAT, SAT, or VSR, adjusting for age and sex (P<0.001), were genotyped in the remaining 961 Hispanic samples. The entire Hispanic cohort (n=1,190) was then tested for association, adjusting for age, sex, site of recruitment, and admixture estimates (stage 2). In stage 3, additional SNPs were genotyped in four genic regions showing evidence of association in stage 2. Several SNPs were associated in the GWAS (P<1x10(-5)) and were confirmed to be significantly associated in the entire Hispanic cohort (P<0.01), including: rs7543757 for VAT, rs4754373 and rs11212913 for SAT, and rs4541696 and rs4134351 for VSR. Numerous SNPs were associated with multiple adiposity phenotypes. Targeted analysis of four genes whose SNPs were significant in stage 2 suggests candidate genes for influencing the distribution (RGS6) and amount of adiposity (NGEF). Several candidate loci, including RGS6 and NGEF, are associated with CT-derived adipose fat measures in Hispanic Americans in a three-stage genetic association study.
我们研究了与胰岛素抵抗动脉粥样硬化研究家族研究（IRASFS）中西班牙裔人群的计算机断层扫描（CT）衍生的肥胖指标相关的候选基因组区域。在来自科罗拉多州圣路易斯谷和德克萨斯州圣安东尼奥的 92 个家庭的 1190 名西班牙裔个体中，我们测量了 CT 衍生的内脏脂肪组织（VAT）、皮下脂肪组织（SAT）和内脏：皮下比（VSR）。使用 Illumina HumanHap 300 BeadChip（约 317K 个单核苷酸多态性（SNP））在来自圣安东尼奥地点的 229 名个体中完成了全基因组关联研究（GWAS）（第 1 阶段）。在总共 297 个具有与 VAT、SAT 或 VSR 相关证据的 SNP 中，调整年龄和性别（P<0.001）后，在其余 961 名西班牙裔样本中进行了基因分型。整个西班牙裔队列（n=1190）然后进行了关联测试，调整了年龄、性别、招募地点和混合估计（第 2 阶段）。在第 3 阶段，在第 2 阶段显示出关联证据的四个基因区域中进一步基因分型了其他 SNP。在 GWAS 中发现了几个 SNP 具有关联（P<1x10(-5))，并且在整个西班牙裔队列中被证实具有显著关联（P<0.01），包括：VAT 的 rs7543757、SAT 的 rs4754373 和 rs11212913 以及 VSR 的 rs4541696 和 rs4134351。许多 SNP 与多种肥胖表型相关。对第 2 阶段中 SNP 显著的四个基因的靶向分析表明了影响分布（RGS6）和脂肪量（NGEF）的候选基因。包括 RGS6 和 NGEF 在内的几个候选基因座与西班牙裔美国人的 CT 衍生脂肪测量值相关，这是一项三阶段遗传关联研究的结果。
